Familial Mediterranean fever: High gene frequency and heterogeneous disease among an Israeli-Arab population

Objective. Familial Mediterranean fever (FMF) is an autosomal recessive disease that primarily affects non-Ashkenazi Jews, Armenians, Arabs, and Turks. The FMF (MEFV) gene responsible for the disease has been recently identified. Four missense mutations in exon 10 of the FMF gene seem to account for 86% of the DNA variations identified in patients with FMF. We conducted a phenotype/genotype correlation study in a homogenous population of Israeli-Moslem Arab patients with FMF and performed a mutational screening analysis on DNA samples from healthy individuals of this ethnic group. Methods. Sixty-five patients clinically diagnosed as having FMF underwent molecular genetic studies using polymerase chain reaction and restriction endonuclease digestion methods to detect the presence of the 4 mutations (M694V, V726A, M680I, M694I). We then correlated the presence of each mutation with age of onset, clinical manifestations, and disease severity; patients whose allelic combination included M694V were then excluded from further statistical analysis, since the association of severe disease with the M694V allele has already been shown. In addition, we screened for FMF mutations the DNA samples from 318 healthy Moslem Arab individuals for the presence of these mutations. Results. Among the 65 patients who were clinically diagnosed as having FMF, 78.5% had one or 2 mutation-bearing chromosomes. The most prevalent mutation was V726A, followed by M680I, M694V, and M694I. No significant difference in phenotypic characteristics was found between the patients with the diverse mutations. The total carrier frequency for the 4 mutations was 10.4% (95% confidence interval 0.07 to 0.137). Conclusion. A high FMF gene frequency was found among an Israeli-Moslem Arab population. Among the FMF patients from this ethnic group, several mutations were detected, none of which was found to correlate with a severe course of the disease.